DESCRIPTION (Applicant's Abstract): Orphanin FQ, heptadecapeptide, is the natural ligand for a newly identified opioid related receptor. Using a tritium labeled form of this peptide, a radioreceptor binding assay has been developed using rat brain homogenates. Synthetic combinatiorial libraries, peptidomimietic and peptide libraries will be examined. Examples of the heterocyclic libraries include bicyclic guanidines, substitute isoquinilones, indole-imidazoles, quinazolinones, cyclic ureas and hydantoins. New libraries synthesized during the course of the study will also be screened. A determination of the agonist and antagonist properties of any new ligands identified will be made. Any identified antagonists or agonists will be investigated as potential therapeutics. From in vivo studies, Orphanin FQ has been shown to induce hypersensitivity to pain, has been described as having anti-opiate activity and has been shown to be a water diuretic. Three different in vitro assays will be employed: a cAMP accumulation assay, a GTP binding assay and a mouse was deferens contraction inhibition assay. Antagonist will be studies for their ability inhibit the hyperalgesic effects of Orphanin FQ. Identified agonist compounds will be investigated for their ability to induce delayed analgesia as observed by Orphanin FQ (or its metabolites), and will be investigated for ability to induce water diuresis.